CA2633186C - 2-adamantylurea derivatives as selective 11.beta.-hsd1 inhibitors - Google Patents
2-adamantylurea derivatives as selective 11.beta.-hsd1 inhibitors Download PDFInfo
- Publication number
- CA2633186C CA2633186C CA2633186A CA2633186A CA2633186C CA 2633186 C CA2633186 C CA 2633186C CA 2633186 A CA2633186 A CA 2633186A CA 2633186 A CA2633186 A CA 2633186A CA 2633186 C CA2633186 C CA 2633186C
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- CA
- Canada
- Prior art keywords
- adamantan
- urea
- phenyl
- methyl
- acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000003112 inhibitor Substances 0.000 title claims description 41
- LQXUPNMWDYTSKT-UHFFFAOYSA-N 2-adamantylurea Chemical class C1C(C2)CC3CC1C(NC(=O)N)C2C3 LQXUPNMWDYTSKT-UHFFFAOYSA-N 0.000 title abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 181
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 52
- 238000011282 treatment Methods 0.000 claims abstract description 43
- 208000035475 disorder Diseases 0.000 claims abstract description 33
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 29
- 206010020772 Hypertension Diseases 0.000 claims abstract description 20
- 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 20
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 20
- 208000008589 Obesity Diseases 0.000 claims abstract description 19
- 201000010099 disease Diseases 0.000 claims abstract description 19
- 235000020824 obesity Nutrition 0.000 claims abstract description 19
- 150000002632 lipids Chemical class 0.000 claims abstract description 15
- 230000002265 prevention Effects 0.000 claims abstract description 15
- 208000001145 Metabolic Syndrome Diseases 0.000 claims abstract description 13
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims abstract description 13
- 208000010877 cognitive disease Diseases 0.000 claims abstract description 13
- 208000026278 immune system disease Diseases 0.000 claims abstract description 12
- 208000010412 Glaucoma Diseases 0.000 claims abstract description 10
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 9
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 9
- 230000036506 anxiety Effects 0.000 claims abstract description 9
- 239000004202 carbamide Substances 0.000 claims description 128
- 150000003839 salts Chemical class 0.000 claims description 55
- 239000000203 mixture Substances 0.000 claims description 54
- -1 benzdioxinyl Chemical group 0.000 claims description 50
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims description 44
- 239000003862 glucocorticoid Substances 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 35
- 239000012453 solvate Substances 0.000 claims description 30
- 201000001320 Atherosclerosis Diseases 0.000 claims description 25
- 229960000890 hydrocortisone Drugs 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 21
- 238000002360 preparation method Methods 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 16
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 16
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 16
- 230000001404 mediated effect Effects 0.000 claims description 15
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 14
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 13
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 13
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 13
- 239000008103 glucose Substances 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 230000004770 neurodegeneration Effects 0.000 claims description 10
- 230000003955 neuronal function Effects 0.000 claims description 10
- 208000028698 Cognitive impairment Diseases 0.000 claims description 9
- 206010033645 Pancreatitis Diseases 0.000 claims description 9
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 9
- 208000017442 Retinal disease Diseases 0.000 claims description 9
- 206010038923 Retinopathy Diseases 0.000 claims description 9
- 201000001421 hyperglycemia Diseases 0.000 claims description 9
- 208000017169 kidney disease Diseases 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 9
- 201000001119 neuropathy Diseases 0.000 claims description 9
- 230000007823 neuropathy Effects 0.000 claims description 9
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 9
- 208000037803 restenosis Diseases 0.000 claims description 9
- 230000002792 vascular Effects 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 7
- 229960003805 amantadine Drugs 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 7
- 239000002552 dosage form Substances 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 6
- 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 6
- 206010024229 Leprosy Diseases 0.000 claims description 6
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 claims description 6
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 201000009104 prediabetes syndrome Diseases 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 201000008827 tuberculosis Diseases 0.000 claims description 6
- 208000001280 Prediabetic State Diseases 0.000 claims description 5
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- LNNXQSCOUWYAJI-UHFFFAOYSA-N 2-(2-adamantylcarbamoylamino)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 LNNXQSCOUWYAJI-UHFFFAOYSA-N 0.000 claims description 4
- UCDGZQHAOAGGSC-UHFFFAOYSA-N 4-(2-adamantylcarbamoylamino)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 UCDGZQHAOAGGSC-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 239000000969 carrier Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000001425 triazolyl group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
- HISDZQGFUOZNDQ-UHFFFAOYSA-N methyl 3-(2-adamantylcarbamoylamino)-2-methylbenzoate Chemical compound COC(=O)C1=CC=CC(NC(=O)NC2C3CC4CC(C3)CC2C4)=C1C HISDZQGFUOZNDQ-UHFFFAOYSA-N 0.000 claims description 3
- RHMXRUDDABBEME-UHFFFAOYSA-N n-(2-adamantyl)piperidine-1-carboxamide Chemical compound C1C2CC(C3)CC1CC3C2NC(=O)N1CCCCC1 RHMXRUDDABBEME-UHFFFAOYSA-N 0.000 claims description 3
- CRBXJXAUPUPCEV-UHFFFAOYSA-N n-(2-adamantyl)pyrrolidine-1-carboxamide Chemical compound C1C2CC(C3)CC1CC3C2NC(=O)N1CCCC1 CRBXJXAUPUPCEV-UHFFFAOYSA-N 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- NVEGDEXHKTWRLQ-UHFFFAOYSA-N 1-(3-acetylphenyl)-3-(2-adamantyl)urea Chemical compound CC(=O)C1=CC=CC(NC(=O)NC2C3CC4CC(C3)CC2C4)=C1 NVEGDEXHKTWRLQ-UHFFFAOYSA-N 0.000 claims description 2
- HIBKTHKOTUYFGE-UHFFFAOYSA-N 1-(4-acetylphenyl)-3-(2-adamantyl)urea Chemical compound C1=CC(C(=O)C)=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 HIBKTHKOTUYFGE-UHFFFAOYSA-N 0.000 claims description 2
- VBHCPGFCIQDXGZ-UHFFFAOYSA-N 1-isocyanatoadamantane Chemical compound C1C(C2)CC3CC2CC1(N=C=O)C3 VBHCPGFCIQDXGZ-UHFFFAOYSA-N 0.000 claims description 2
- SFUUVLHESQUGIP-UHFFFAOYSA-N 3-(2-adamantylcarbamoylamino)-2-methylbenzoic acid Chemical compound C1=CC=C(C(O)=O)C(C)=C1NC(=O)NC1C(C2)CC3CC2CC1C3 SFUUVLHESQUGIP-UHFFFAOYSA-N 0.000 claims description 2
- GRUMNFYICOFFTR-UHFFFAOYSA-N butyl 4-(2-adamantylcarbamoylamino)benzoate Chemical compound C1=CC(C(=O)OCCCC)=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 GRUMNFYICOFFTR-UHFFFAOYSA-N 0.000 claims description 2
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 claims description 2
- SVKLJEIWBGLACZ-UHFFFAOYSA-N dimethyl 5-(2-adamantylcarbamoylamino)benzene-1,3-dicarboxylate Chemical compound COC(=O)C1=CC(C(=O)OC)=CC(NC(=O)NC2C3CC4CC(C3)CC2C4)=C1 SVKLJEIWBGLACZ-UHFFFAOYSA-N 0.000 claims description 2
- JSDUCZAKMONTIB-UHFFFAOYSA-N ethyl 2-(2-adamantylcarbamoylamino)benzoate Chemical compound CCOC(=O)C1=CC=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 JSDUCZAKMONTIB-UHFFFAOYSA-N 0.000 claims description 2
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 2
- 239000012948 isocyanate Substances 0.000 claims description 2
- 150000002513 isocyanates Chemical class 0.000 claims description 2
- AABCXGCXOGVGAT-UHFFFAOYSA-N methyl 2-(2-adamantylcarbamoylamino)benzoate Chemical compound COC(=O)C1=CC=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 AABCXGCXOGVGAT-UHFFFAOYSA-N 0.000 claims description 2
- FZAGSBYABQTKAE-UHFFFAOYSA-N methyl 3-(2-adamantylcarbamoylamino)benzoate Chemical compound COC(=O)C1=CC=CC(NC(=O)NC2C3CC4CC(C3)CC2C4)=C1 FZAGSBYABQTKAE-UHFFFAOYSA-N 0.000 claims description 2
- SYGYYGCRTPBARB-UHFFFAOYSA-N methyl 4-(2-adamantylcarbamoylamino)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 SYGYYGCRTPBARB-UHFFFAOYSA-N 0.000 claims description 2
- YFROBIHDXYYVKB-UHFFFAOYSA-N n-(2-adamantyl)-3-methylpiperidine-1-carboxamide Chemical compound C1C(C)CCCN1C(=O)NC1C(C2)CC3CC2CC1C3 YFROBIHDXYYVKB-UHFFFAOYSA-N 0.000 claims description 2
- 230000000644 propagated effect Effects 0.000 claims description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 claims description 2
- HDLFKJKNXISKAS-UHFFFAOYSA-N 1-(2-adamantyl)-3-(1-phenylethyl)urea Chemical compound C1C2CC(C3)CC1CC3C2NC(=O)NC(C)C1=CC=CC=C1 HDLFKJKNXISKAS-UHFFFAOYSA-N 0.000 claims 1
- FVNWRVVESGQORO-UHFFFAOYSA-N 1-(2-adamantyl)-3-(1h-1,2,4-triazol-5-yl)urea Chemical compound C1C2CC(C3)CC1CC3C2NC(=O)NC=1N=CNN=1 FVNWRVVESGQORO-UHFFFAOYSA-N 0.000 claims 1
- FRRHMLGKNPFRKT-UHFFFAOYSA-N 1-(2-adamantyl)-3-(2,3,4-trifluorophenyl)urea Chemical compound FC1=C(F)C(F)=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 FRRHMLGKNPFRKT-UHFFFAOYSA-N 0.000 claims 1
- JLDSGFSBCFRCOZ-UHFFFAOYSA-N 1-(2-adamantyl)-3-(2,3-dichlorophenyl)urea Chemical compound ClC1=CC=CC(NC(=O)NC2C3CC4CC(C3)CC2C4)=C1Cl JLDSGFSBCFRCOZ-UHFFFAOYSA-N 0.000 claims 1
- QXGXSTVRMCZUPB-UHFFFAOYSA-N 1-(2-adamantyl)-3-(2,3-dihydro-1h-inden-1-yl)urea Chemical compound C1C(CC2C3)CC3CC1C2NC(=O)NC1C2=CC=CC=C2CC1 QXGXSTVRMCZUPB-UHFFFAOYSA-N 0.000 claims 1
- CEWWOKFUACKBRX-UHFFFAOYSA-N 1-(2-adamantyl)-3-(2,4,5-trimethylphenyl)urea Chemical compound C1=C(C)C(C)=CC(C)=C1NC(=O)NC1C(C2)CC3CC2CC1C3 CEWWOKFUACKBRX-UHFFFAOYSA-N 0.000 claims 1
- XAUWQLDYBQZWBH-UHFFFAOYSA-N 1-(2-adamantyl)-3-(2,4-dibromophenyl)urea Chemical compound BrC1=CC(Br)=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 XAUWQLDYBQZWBH-UHFFFAOYSA-N 0.000 claims 1
- KMAKOBVREGCILP-UHFFFAOYSA-N 1-(2-adamantyl)-3-(2,4-difluorophenyl)urea Chemical compound FC1=CC(F)=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 KMAKOBVREGCILP-UHFFFAOYSA-N 0.000 claims 1
- STUFNGZBOINZIW-UHFFFAOYSA-N 1-(2-adamantyl)-3-(2,4-dimethoxyphenyl)urea Chemical compound COC1=CC(OC)=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 STUFNGZBOINZIW-UHFFFAOYSA-N 0.000 claims 1
- NZLDRGNGLFJOQX-UHFFFAOYSA-N 1-(2-adamantyl)-3-(2,5-dimethoxyphenyl)urea Chemical compound COC1=CC=C(OC)C(NC(=O)NC2C3CC4CC(C3)CC2C4)=C1 NZLDRGNGLFJOQX-UHFFFAOYSA-N 0.000 claims 1
- VZMHGAIGFTXGJU-UHFFFAOYSA-N 1-(2-adamantyl)-3-(2,6-dichloropyridin-4-yl)urea Chemical compound ClC1=NC(Cl)=CC(NC(=O)NC2C3CC4CC(C3)CC2C4)=C1 VZMHGAIGFTXGJU-UHFFFAOYSA-N 0.000 claims 1
- GNIWEUBKPCRCPK-UHFFFAOYSA-N 1-(2-adamantyl)-3-(2-ethoxyphenyl)urea Chemical compound CCOC1=CC=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 GNIWEUBKPCRCPK-UHFFFAOYSA-N 0.000 claims 1
- HAQDTZJMOBBBNZ-UHFFFAOYSA-N 1-(2-adamantyl)-3-(2-fluoro-5-methylphenyl)urea Chemical compound CC1=CC=C(F)C(NC(=O)NC2C3CC4CC(C3)CC2C4)=C1 HAQDTZJMOBBBNZ-UHFFFAOYSA-N 0.000 claims 1
- HIEKNKPTNVLWFN-UHFFFAOYSA-N 1-(2-adamantyl)-3-(2-hydroxy-1-phenylethyl)urea Chemical compound C1C2CC(C3)CC1CC3C2NC(=O)NC(CO)C1=CC=CC=C1 HIEKNKPTNVLWFN-UHFFFAOYSA-N 0.000 claims 1
- RWMQXYXVIIDHTP-UHFFFAOYSA-N 1-(2-adamantyl)-3-(2-methoxyphenyl)urea Chemical compound COC1=CC=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 RWMQXYXVIIDHTP-UHFFFAOYSA-N 0.000 claims 1
- VTNDMIUKGCALRD-UHFFFAOYSA-N 1-(2-adamantyl)-3-(2-methylsulfanylphenyl)urea Chemical compound CSC1=CC=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 VTNDMIUKGCALRD-UHFFFAOYSA-N 0.000 claims 1
- MMIBYMVOUXRCPS-UHFFFAOYSA-N 1-(2-adamantyl)-3-(2-phenoxyphenyl)urea Chemical compound C1C2CC(C3)CC1CC3C2NC(=O)NC1=CC=CC=C1OC1=CC=CC=C1 MMIBYMVOUXRCPS-UHFFFAOYSA-N 0.000 claims 1
- QUHXXAPBXGLATI-UHFFFAOYSA-N 1-(2-adamantyl)-3-(2-phenylethyl)urea Chemical compound C1C2CC(C3)CC1CC3C2NC(=O)NCCC1=CC=CC=C1 QUHXXAPBXGLATI-UHFFFAOYSA-N 0.000 claims 1
- HPAIFPMAFUHUPU-UHFFFAOYSA-N 1-(2-adamantyl)-3-(2-thiophen-2-ylethyl)urea Chemical compound C1C2CC(C3)CC1CC3C2NC(=O)NCCC1=CC=CS1 HPAIFPMAFUHUPU-UHFFFAOYSA-N 0.000 claims 1
- MBYSWEPHTLVFQB-UHFFFAOYSA-N 1-(2-adamantyl)-3-(3,4-difluorophenyl)urea Chemical compound C1=C(F)C(F)=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 MBYSWEPHTLVFQB-UHFFFAOYSA-N 0.000 claims 1
- GOEILSVPOKTOJH-UHFFFAOYSA-N 1-(2-adamantyl)-3-(3,4-dimethoxyphenyl)urea Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 GOEILSVPOKTOJH-UHFFFAOYSA-N 0.000 claims 1
- DVSAPXJVQZJLRW-UHFFFAOYSA-N 1-(2-adamantyl)-3-(3,4-dimethylphenyl)urea Chemical compound C1=C(C)C(C)=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 DVSAPXJVQZJLRW-UHFFFAOYSA-N 0.000 claims 1
- XUKMHXYUNAFVCL-UHFFFAOYSA-N 1-(2-adamantyl)-3-(3,5-dichloro-2-hydroxy-4-methylphenyl)urea Chemical compound OC1=C(Cl)C(C)=C(Cl)C=C1NC(=O)NC1C(C2)CC3CC2CC1C3 XUKMHXYUNAFVCL-UHFFFAOYSA-N 0.000 claims 1
- SHWWRXRJPOAFKI-UHFFFAOYSA-N 1-(2-adamantyl)-3-(3,5-dimethoxyphenyl)urea Chemical compound COC1=CC(OC)=CC(NC(=O)NC2C3CC4CC(C3)CC2C4)=C1 SHWWRXRJPOAFKI-UHFFFAOYSA-N 0.000 claims 1
- XDSMNUCCNDGLTP-UHFFFAOYSA-N 1-(2-adamantyl)-3-(3-chloro-4-methoxyphenyl)urea Chemical compound C1=C(Cl)C(OC)=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 XDSMNUCCNDGLTP-UHFFFAOYSA-N 0.000 claims 1
- YDSXRGWTSJWFPL-UHFFFAOYSA-N 1-(2-adamantyl)-3-(3-chloro-4-methylphenyl)urea Chemical compound C1=C(Cl)C(C)=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 YDSXRGWTSJWFPL-UHFFFAOYSA-N 0.000 claims 1
- IBJGGRFFYPYLHK-UHFFFAOYSA-N 1-(2-adamantyl)-3-(3-chlorophenyl)urea Chemical compound ClC1=CC=CC(NC(=O)NC2C3CC4CC(C3)CC2C4)=C1 IBJGGRFFYPYLHK-UHFFFAOYSA-N 0.000 claims 1
- IFAOIBNIQILFDO-UHFFFAOYSA-N 1-(2-adamantyl)-3-(3-ethylphenyl)urea Chemical compound CCC1=CC=CC(NC(=O)NC2C3CC4CC(C3)CC2C4)=C1 IFAOIBNIQILFDO-UHFFFAOYSA-N 0.000 claims 1
- CDTHBOOCDGZRAS-UHFFFAOYSA-N 1-(2-adamantyl)-3-(3-fluoro-4-methylphenyl)urea Chemical compound C1=C(F)C(C)=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 CDTHBOOCDGZRAS-UHFFFAOYSA-N 0.000 claims 1
- MAMPNMMYDWIFKC-UHFFFAOYSA-N 1-(2-adamantyl)-3-(3-methoxyphenyl)urea Chemical compound COC1=CC=CC(NC(=O)NC2C3CC4CC(C3)CC2C4)=C1 MAMPNMMYDWIFKC-UHFFFAOYSA-N 0.000 claims 1
- RFJFPGDIOORZID-UHFFFAOYSA-N 1-(2-adamantyl)-3-(3-methyl-5-phenyl-1,2-oxazol-4-yl)urea Chemical compound C1C2CC(C3)CC1CC3C2NC(=O)NC=1C(C)=NOC=1C1=CC=CC=C1 RFJFPGDIOORZID-UHFFFAOYSA-N 0.000 claims 1
- AEUKVBPDYFEQGB-UHFFFAOYSA-N 1-(2-adamantyl)-3-(3-methylsulfanylphenyl)urea Chemical compound CSC1=CC=CC(NC(=O)NC2C3CC4CC(C3)CC2C4)=C1 AEUKVBPDYFEQGB-UHFFFAOYSA-N 0.000 claims 1
- RQJAIFSYDJCQNK-UHFFFAOYSA-N 1-(2-adamantyl)-3-(4-bromo-2-fluorophenyl)urea Chemical compound FC1=CC(Br)=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 RQJAIFSYDJCQNK-UHFFFAOYSA-N 0.000 claims 1
- KDHTWDAAPXJUJB-UHFFFAOYSA-N 1-(2-adamantyl)-3-(4-bromophenyl)urea Chemical compound C1=CC(Br)=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 KDHTWDAAPXJUJB-UHFFFAOYSA-N 0.000 claims 1
- YGNJBVZMHGPECX-UHFFFAOYSA-N 1-(2-adamantyl)-3-(4-butoxyphenyl)urea Chemical compound C1=CC(OCCCC)=CC=C1NC(=O)NC1C(C2)CC3CC2CC1C3 YGNJBVZMHGPECX-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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EP05292724.1 | 2005-12-16 | ||
EP05292724A EP1801098A1 (de) | 2005-12-16 | 2005-12-16 | 2-Adamantylharnstoff Derivative als selektive 11B-HSD1 Inhibitoren |
PCT/EP2006/011156 WO2007068330A1 (en) | 2005-12-16 | 2006-11-22 | 2-ADAMANTYLUREA DERIVATIVES AS SELECTIVE 11β-HSD1 INHIBITORS |
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EP (2) | EP1801098A1 (de) |
JP (1) | JP5356825B2 (de) |
KR (1) | KR101394586B1 (de) |
CN (1) | CN101331114B (de) |
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SI (1) | SI1960352T1 (de) |
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- 2006-11-22 EP EP06818709.5A patent/EP1960352B1/de active Active
- 2006-11-22 SI SI200631675T patent/SI1960352T1/sl unknown
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- 2006-11-22 PT PT68187095T patent/PT1960352E/pt unknown
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CA2633186A1 (en) | 2007-06-21 |
PT1960352E (pt) | 2013-10-31 |
EA200801426A1 (ru) | 2008-10-30 |
BRPI0619839B8 (pt) | 2021-05-25 |
US8188288B2 (en) | 2012-05-29 |
DK1960352T3 (da) | 2013-10-28 |
EP1960352B1 (de) | 2013-08-07 |
IL192053A0 (en) | 2008-12-29 |
WO2007068330A1 (en) | 2007-06-21 |
BRPI0619839A2 (pt) | 2011-10-18 |
KR20080079317A (ko) | 2008-08-29 |
AR058546A1 (es) | 2008-02-13 |
US20090227631A1 (en) | 2009-09-10 |
KR101394586B1 (ko) | 2014-05-12 |
AU2006326703B2 (en) | 2012-02-23 |
CY1114660T1 (el) | 2016-10-05 |
ZA200806148B (en) | 2009-06-24 |
JP2009525262A (ja) | 2009-07-09 |
US8466200B2 (en) | 2013-06-18 |
ES2434077T3 (es) | 2013-12-13 |
SI1960352T1 (sl) | 2013-12-31 |
PL1960352T3 (pl) | 2013-12-31 |
US20120172396A1 (en) | 2012-07-05 |
JP5356825B2 (ja) | 2013-12-04 |
IL192053A (en) | 2014-01-30 |
CN101331114A (zh) | 2008-12-24 |
EA017923B1 (ru) | 2013-04-30 |
BRPI0619839B1 (pt) | 2021-01-12 |
EP1960352A1 (de) | 2008-08-27 |
EP1801098A1 (de) | 2007-06-27 |
CN101331114B (zh) | 2013-08-07 |
AU2006326703A1 (en) | 2007-06-21 |
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